The present invention relates to the use of quaternary N-benzyl-N-{2-[2-((1S,5S)-6,6-dimethylbicyclo[3,1,1]hept-2-yl)-ethoxy]-eth yl}-morpholinium salts for the prophylaxis and treatment of blood circulation disorders in the peripheral, in particular in the microvascular, region of the stomach or intestinal walls and/or for prophylaxis and treatment of damage to the gastrointestinal tract in larger mammals, particularly in humans, which is caused by gastrotoxic doses of medicaments or chemicals. In particular, the invention relates to the prophylaxis and treatment of damage to the stomach or intestinal tract which may be caused by frequent consumption of nonsteroid antiinflammatory medicines, for instance in rheumatism therapy.
The non-steroid antiphlogistic agents and antirheumatic agents (=non-steroid anti-inflammatory drugs, abbreviated hereinafter as NSAIDs) include, inter alia, substituted benzoic acid derivatives, for instance salicylic acid derivatives such as acetylsalicylic acid (aspirin) or salicylamide; anthranilic acid derivatives such as flufenamic acid; arylacetic acid derivatives, for instance substituted phenylacetic acid derivatives such as Diclofenac or Ibufenac, substituted indole acetic acid derivatives such as indomethacine or substituted 2-phenylpropionic acid derivatives such as Ibuprofen; quinoline carboxylic acid derivatives; pyrazolindione derivatives, for instance diphenylpyrazolindione derivatives such as phenylbutazone or oxyfenbutazone; phenylpyrazolone derivatives such as phenazone, aminophenazone or propiphenazone; and oxicam derivatives such as piroxicam or tenoxicam.
It is known that NSAIDs have cyclooxygenase-inhibiting effects and thus have an inhibitive effect on endogenous prostaglandin formation. Prostaglandins are found in relatively high concentrations in the walls of the gastrointestinal tract. They play a major role in gastrointestinal physiology and affect a large number of functions in the stomach and intestinal tract. For instance, in addition to inhibiting the secretion of acid, the prostaglandins also enhance the circulation of blood in the stomach mucosa and exhibit mucosa-protective properties.
It is known that, particularly in long-term use, NSAIDs lead to serious damage to the mucosa and walls of the stomach or intestinal tract ranging, for example, from hemorrhages up to very serious stomach bleeding and lesions. H.sub.2 -receptor-antagonistic substances, which are otherwise successfully used as ulcer therapy agents, cannot effectively prevent NSAID-induced damage to the stomach and intestinal tract.
Quaternary N-benzyl-N-{2-[2-((1S,5S)-6,6-dimethyl-bicyclo[3,1,1]hept-2-yl)-ethoxy]-et hyl}-morpholinium salts having spasmolytic properties are known from U.S. Pat. No. 3,845,048 (=French Patent No. 2,097,032). Pinaverium bromide (=N-(2-bromo-4,5-dimethoxybenzyl)-N-{2-[2-((1S,5S)6,6-dimethylbicyclo [3,1,1]hept-2-yl)-ethoxy]-ethyl}-morpholinium bromide), for instance, which falls within the scope of the aforementioned patent, is commercially available as a spasmolytic under the trade name "Dicetel.TM.".